Prevalence and Risk for Bundle Branch Block, Atrioventricular Block and Pacemaker Implantation in Spondyloarthritis. A Systematic Review of the Literature.

Objective: To evaluate the evidence regarding the prevalence and risk of bundle branch block (BBB), atrioventricular block (AVB) and pacemaker implantation (PMI) in patients with spondyloarthritis compared to a control group without spondyloarthritis. Methods: A systematic review of the literature was performed using Pubmed (Medline), EMBASE (Elsevier) and Cochrane Library (Wiley) databases until December 2021. The prevalence and risk for AVB, BBB and PMI were analyzed. Cohort, case control and cross-sectional studies in patients ≥18 years meeting the classification criteria for spondyloarthritis were included. The Odds ratio (OR), risk ratio (RR), or Hazard ratio (HR) and prevalence difference were considered as outcomes. Data was synthesized in a previously defined extraction form which included a risk of bias assessment using the Newcastle-Ottawa Scale. Results: In total, eight out of 374 studies were included. None of the studies provided results regarding the risk of low grade AVB and BBB in SpA patients. Only indirect results comparing prevalences from low to medium quality studies were found. According to population based registries, the sex and age adjusted HR of AVB was 2.3 (95% CI 1.6-3.3) in ankylosing spondylitis, 2.9 (95% CI 1.8-4.7) in undifferentiated spondyloarthritis and 1.5 (95% CI 1.1 a 1.9) in psoriatic arthritis. The absolute risk for AVB was 0.4% (moderate to high; 95% CI 0.34%-0.69%) for AS, 0.33% (moderate to high; 95% CI 0.21%-0.53%) for uSpA and 0.34% (moderate to high; 95% CI 0.26%-0.45%) for PsA.The RR for PMI in AS patients was 1.3 (95% CI 1.16-1.46) for groups aged between 65 and 69 years, 1.33 (95% CI 1.22-1.44) for 70-75 years, 1.24 (95% CI 1.55-1.33) for 75-79 years and 1.11 (95% CI 1.06-1.17) for groups older than 80 years. The absolute risk for PMI in AS patients was 0.7% (moderate to high risk; 95% CI 0.6-0.8%) for groups aged between 65-69, 1.44% (high risk; 95% CI 1.33-1.6%) for 70-75 years, 2.09% (high risk; 95% CI 2.0-2.2%) for 75-79 years and 4.15% (high risk; 95% CI 4.0-4.3%) for groups older than 80 years. Conclusions: Very few cases of low grade AVB and BBB were observed in observational studies. No study evaluated association measures for low grade AVB and BBB but the differences of prevalence were similar in SpA and control groups even though studies lacked the power to detect statistical differences. According to population based registries there was an approximately two fold-increased risk of high grade AVB in SpA patients. RR for PMI was higher in younger age groups.

Valve Abnormalities, Risk Factors for Heart Valve Disease and Valve Replacement Surgery in Spondyloarthritis. A Systematic Review of the Literature.

Objective: Evaluate the evidence on the abnormalities of the aortic root and heart valves, risk and prognostic factors for heart valve disease and valve replacement surgery in spondyloarthritis. Methods: A systematic literature review was performed using Medline, EMBASE and Cochrane databases until July 2021. Prevalence, incidence, risk and prognostic factors for heart valve disease; dimension, morphology, and pathological abnormalities of the valves were analyzed. Patient characteristics (younger age, history of cardiac disease or longer disease duration) and period of realization were considered for the analysis. The SIGN Approach was used for rating the quality of the evidence of the studies. Results: In total, 37 out of 555 studies were included. Overall, the level of evidence was low. The incidence of aortic insufficiency was 2.5-3.9‰. Hazard Ratio for aortic insufficiency was 1.8-2.0. Relative risk for aortic valve replacement surgery in ankylosing spondylitis patients was 1.22-1.46. Odds ratio for aortic insufficiency was 1.07 for age and 1.05 for disease duration. Mitral valve abnormalities described were mitral valve prolapse, calcification, and thickening. Aortic valve abnormalities described were calcification, thickening and an echocardiographic "subaortic bump." Abnormalities of the aorta described were thickening of the wall and aortic root dilatation. The most common microscopic findings were scarring of the adventitia, lymphocytic infiltration, and intimal proliferation. Conclusions: A higher prevalence and risk of aortic valve disease is observed in patients with ankylosing spondylitis. Studies were heterogeneous and analysis was not adjusted by potential confounders. Most studies did not define accurate outcomes and may have detected small effects as being statistically significant.

Efficacy of belimumab in Primary Sjögren's syndrome: A systematic review / Eficacia del belimumab en el síndrome de Sjögren primario: una revisión sistemática

Objective: To evaluate the efficacy and safety of belimumab in patients with Primary Sjögren's syndrome (pSS). Methods: The search included manuscripts assessing the efficacy or safety of belimumab in patients with pSS (American-European Consensus Criteria 2002) published between 2004 and 2017 in MEDLINE, EMBASE or Cochrane databases. Two reviewers independently selected the articles, extracted data and evaluated the quality of the evidence following Scottish Intercollegiate Guidelines Network (SIGN) recommendation grades. Results: Out of 135 citations, only 3 articles were included. All of them publishing results from the same study at different time points including 28 patients. At week 28 improvement was reported for visual analogue scale (VAS) dryness score and glandular manifestations in 37% and 77% of patients, respectively, which persisted at week 52 (W52). Belimumab was well tolerated and safely administered. Conclusion: Published evidence to determine the efficacy of belimumab in pSS is limited. Belimumab seems to be effective to reduce systemic activity, parotid enlargement, lymphadenopathies, articular manifestation and B cell biomarkers.(AU)

Objetivo: Evaluar la eficacia y la seguridad de belimumab en pacientes con síndrome de Sjögren primario (SSp). Métodos: La búsqueda incluyó manuscritos que evaluaban la eficacia o seguridad de belimumab en pacientes con SSp (Criterios Europeo-Americanos del 2002) publicados entre 2004 y 2007 en MEDLINE, EMBASE o Cochrane database. Dos revisores independientes seleccionaron los artículos, extrajeron los datos y evaluaron la calidad de la evidencia según los grados de recomendación de la Scottish Intercollegiate Guidelines Network (SIGN). Resultados: De 135 artículos se incluyeron 3. Todos publicaban resultados del mismo estudio en diferentes momentos, incluyéndose 28 pacientes. En la semana 28 presentaban una mejoría en la puntuación de sequedad en la escala analógica visual (VAS) y en las manifestaciones glandulares un 37 y 77% de los pacientes, respectivamente, que persistieron en la 52. La administración de belimumab fue segura y bien tolerada. Conclusión: Belimumab parece ser efectivo para reducir la actividad sistémica, el aumento parotídeo, las linfadenopatías, las manifestaciones articulares y los biomarcadores de células B, aunque con evidencia limitada.(AU)

Efficacy of belimumab in Primary Sjögren's syndrome: A systematic review.

OBJECTIVE: To evaluate the efficacy and safety of belimumab in patients with Primary Sjögren's syndrome (pSS). METHODS: The search included manuscripts assessing the efficacy or safety of belimumab in patients with pSS (American-European Consensus Criteria 2002) published between 2004 and 2017 in MEDLINE, EMBASE or Cochrane databases. Two reviewers independently selected the articles, extracted data and evaluated the quality of the evidence following Scottish Intercollegiate Guidelines Network (SIGN) recommendation grades. RESULTS: Out of 135 citations, only 3 articles were included. All of them publishing results from the same study at different time points including 28 patients. At week 28 improvement was reported for visual analogue scale (VAS) dryness score and glandular manifestations in 37% and 77% of patients, respectively, which persisted at week 52 (W52). Belimumab was well tolerated and safely administered. CONCLUSION: Published evidence to determine the efficacy of belimumab in pSS is limited. Belimumab seems to be effective to reduce systemic activity, parotid enlargement, lymphadenopathies, articular manifestation and B cell biomarkers.

Eficacia de los fármacos antirreumáticos modificadores de la enfermedad sintéticos en artritis psoriásica: una revisión sistemática / Effectiveness of conventional disease-modifying antirheumatic drugs in psoriatic arthritis: a systematic review

Antecedentes. Dada la heterogeneidad clínica de la artritis psoriásica (APs), se han elaborado recomendaciones por grupos internacionales para orientar las decisiones terapéuticas del reumatólogo. Esta revisión sistemática (RS) tiene el objetivo de evaluar la evidencia sobre la eficacia de los FAME en APs. Métodos. Búsqueda bibliográfica en Medline, Embase, Cochrane Library, desde 2008 hasta 2014. Se incluyeron RS, EC y estudios observacionales, en pacientes con APs con evaluación de eficacia de FAME sintéticos (metotrexato, sulfasalazina y leflunomida), los siguientes desenlaces: síntomas periféricos; daño estructural radiológico periférico; síntomas axiales; entesopatía por ecografía o resonancia magnética (número de entesis antes y después del estudio); dactilitis, y uveítis. Resultados. Se recuperaron 1.662 documentos para revisar por título y «abstract» (Medline, n=433; Embase n=1.132; Cochrane, n=97), se seleccionaron 48 estudios para su lectura detallada, y se incluyeron 8 estudios. Conclusiones. Ya que los estudios incluidos no son consistentes, y hay argumentos para apoyar la eficacia del metotrexato, la evidencia observada con el tratamiento de FAME en APs no es concluyente (AU)

Background. Due to the clinical heterogeneity of psoriatic arthritis (PsA), recommendations have been developed by international groups to guide therapeutic decisions of the rheumatologist. The objective of the current systematic review (RS) was to evaluate the evidence of efficacy of disease-modifying antirheumatic drugs (DMARDs) in PsA. Methods. Literature search in Medline, EMBASE, Cochrane Library, from 2008 to 2014. We included RS, randomized clinical trials and observational studies, in patients with PsA and an evaluation of efficiency of conventional DMARDs (methotrexate, sulfasalazine, leflunomide), according to the following outcomes: peripheral and axial symptoms; peripheral radiological damage; enthesitis according to power Doppler ultrasound or magnetic resonance imaging (enthesitis count before and after therapy); dactylitis; uveitis. Results. Title and abstract were used to retrieve 1,662 documents for this review (Medline, n=433; EMBASE n=1,132; Cochrane, n=97), and 48 studies were selected for detailed reading; finally, 8 studies were included. Conclusions. Since the studies included are not robust, and there are arguments to support the effectiveness of methotrexate, the evidence observed with the treatment of DMARDs in PsA is not conclusive (AU)

Effectiveness of conventional disease-modifying antirheumatic drugs in psoriatic arthritis: A systematic review. / Eficacia de los fármacos antirreumáticos modificadores de la enfermedad sintéticos en artritis psoriásica: una revisión sistemática.

BACKGROUND: Due to the clinical heterogeneity of psoriatic arthritis (PsA), recommendations have been developed by international groups to guide therapeutic decisions of the rheumatologist. The objective of the current systematic review (RS) was to evaluate the evidence of efficacy of disease-modifying antirheumatic drugs (DMARDs) in PsA. METHODS: Literature search in Medline, EMBASE, Cochrane Library, from 2008 to 2014. We included RS, randomized clinical trials and observational studies, in patients with PsA and an evaluation of efficiency of conventional DMARDs (methotrexate, sulfasalazine, leflunomide), according to the following outcomes: peripheral and axial symptoms; peripheral radiological damage; enthesitis according to power Doppler ultrasound or magnetic resonance imaging (enthesitis count before and after therapy); dactylitis; uveitis. RESULTS: Title and abstract were used to retrieve 1,662 documents for this review (Medline, n=433; EMBASE n=1,132; Cochrane, n=97), and 48 studies were selected for detailed reading; finally, 8 studies were included. CONCLUSIONS: Since the studies included are not robust, and there are arguments to support the effectiveness of methotrexate, the evidence observed with the treatment of DMARDs in PsA is not conclusive.

Switching biological disease-modifying antirheumatic drugs in patients with axial spondyloarthritis: results from a systematic literature review.

OBJECTIVES: First, to investigate if switching biological disease-modifying antirheumatic drugs (bDMARDs) after the failure to prior bDMARD is efficacious in patients with axial spondyloarthritis (axSpA). Second, to evaluate the influence on this efficacy of (1) the reason to discontinue prior tumour necrosis factor inhibitor (TNFi), (2) changing the type of TNFi and (3) changing the target. METHODS: A systematic literature review until January 2017 was performed using Medline, EMBASE and Cochrane databases. Longitudinal studies assessing clinical response after switching bDMARDs in patients with axSpA were analysed. RESULTS: In total, 9 studies out of 1862 retrieved citations were included. Overall, the level of evidence was poor. In these studies, all patients received a TNFi as first bDMARD, 1956 patients switched to a second bDMARD (97% TNFi and 3% interleukin-17 inhibitors (IL-17i)) and 170 to a third bDMARD (all TNFi). Clinical response (Bath Ankylosing Spondylitis Disease Activity Index 50) after a second TNFi was achieved by 25%-56% of patients compared with 50%-72% after the first TNFi. Also, 47% of patients switching to IL-17i after a TNFi responded (Assessment of SpondyloArthritis international Society 40) compared with 66% in those who received IL-17i as first line. The response after switching was not influenced by the reason to discontinue, type of prior TNFi or changing the target. CONCLUSIONS: In patients with axSpA, switching to a second bDMARD (a TNFi or IL-17i) after prior TNFi is efficacious. Nevertheless, the clinical response is lower than the observed in patients naive to bDMARD. So far, the reason to discontinue prior bDMARD or the type of bDMARD has not been identified as predictor of response. Published evidence for switching to a third bDMARD is lacking.

The validity of recommendations from clinical guidelines: a survival analysis.

BACKGROUND: Clinical guidelines should be updated to maintain their validity. Our aim was to estimate the length of time before recommendations become outdated. METHODS: We used a retrospective cohort design and included recommendations from clinical guidelines developed in the Spanish National Health System clinical guideline program since 2008. We performed a descriptive analysis of references, recommendations and resources used, and a survival analysis of recommendations using the Kaplan-Meier method. RESULTS: We included 113 recommendations from 4 clinical guidelines with a median of 4 years since the most recent search (range 3.9-4.4 yr). We retrieved 39 136 references (range 3343-14 787) using an exhaustive literature search, 668 of which were related to the recommendations in our sample. We identified 69 (10.3%) key references, corresponding to 25 (22.1%) recommendations that required updating. Ninety-two percent (95% confidence interval 86.9-97.0) of the recommendations were valid 1 year after their development. This probability decreased at 2 (85.7%), 3 (81.3%) and 4 years (77.8%). INTERPRETATION: Recommendations quickly become outdated, with 1 out of 5 recommendations being out of date after 3 years. Waiting more than 3 years to review a guideline is potentially too long.

Use of clinical practice guidelines and factors related to their uptake: a survey of health professionals in Spain.

RATIONALE, AIMS AND OBJECTIVE: This study aims to assess the use of clinical practice guidelines (CPGs) among health professionals and factors related to their uptake in clinical practice. METHODS: Cross-sectional study based on an online survey conducted among primary care (PC) and hospital-based care (HC) doctors in Spain in 2011. Questionnaire development included adaptation of similar surveys and contextualization through a qualitative study. After a pilot study and review, the final survey contained five domains: demographics, involvement in CPGs, consultation of CPGs, perceptions and attitudes regarding CPGs and Spanish NHS CPGs Programme. Professionals from selected health care centres in seven regions were contacted by email with an invitation and link to the Web-based questionnaire. We analysed between-group differences and explored potential predictors of CPGs use by means of a logistic regression. RESULTS: Six hundred seventy-six doctors responded to the survey (27.7% response rate). 47.1% were PC and 49.5% were HC doctors. 32.5% stated previous involvement in CPGs and 56.5% stated training in research methodology. 67.5% of the surveyed professionals reported using CPGs more than one time per week. The use of a system for classifying the quality of evidence (62.3%) and for grading the strength of the recommendations (58.6%), as well as the use of a rigorous methodology (49.6%), were the most frequently reported aspects related to CPG credibility. The lack of time (56.4%), especially in PC (65.3% versus 49.5% in HC; P < 0.001), and the absence of brief and easily accessible format (42.2%) were the main reported barriers to using CPGs. None of the studied factors showed statistically significant association in the logistic regression model. CONCLUSIONS: Study results suggest that, in general, Spanish doctors trust and use CPGs frequently. To improve uptake by health professionals and to overcome existing barriers, CPGs should be rigorously developed and made accessible at the point-of-care in user-friendly electronic formats. Due to the low response rate, findings should be extrapolated with caution.

Attitudes and perceptions about clinical guidelines: a qualitative study with Spanish physicians.

BACKGROUND: Clinical guidelines (CGs) are popular for healthcare decision making but their acceptability and use by healthcare providers is influenced by numerous factors. Some of these factors are professional-related, such as knowledge and perceptions of and attitudes toward CGs in general. The aim of our study was to evaluate attitudes and perceptions of Spanish physicians towards CGs. METHODS: We coordinated six discussion groups with a total of 46 physicians. The participants were drawn from 12 medical specialties from both specialized and primary care. We recorded the sessions and transcribed the content verbatim. We analyzed the data using an approach based on the grounded theory. RESULTS: We identified two main constructs that defined the physicians' perceptions towards guidelines: knowledge and usefulness. "Knowledge" defined the theoretical meanings of guidelines, while "Usefulness" referred to the pragmatic approach to guidelines. These constructs were interrelated through a series of categories such as confidence, usability, accessibility, dissemination and formats. CONCLUSIONS: In our study, the constructs that impacted most on physician's attitudes to clinical guidelines were knowledge and usefulness. The tension between the theoretical and the pragmatic constructs determined the attitudes and how physicians use guidelines. Groups developing guidelines should ask relevant clinical questions and develop implementable and context specific recommendations. Developers should be explicit and consistent in the development and presentation of recommendations.

Strategies to assess the validity of recommendations: a study protocol.

BACKGROUND: Clinical practice guidelines (CPGs) become quickly outdated and require a periodic reassessment of evidence research to maintain their validity. However, there is little research about this topic. Our project will provide evidence for some of the most pressing questions in this field: 1) what is the average time for recommendations to become out of date?; 2) what is the comparative performance of two restricted search strategies to evaluate the need to update recommendations?; and 3) what is the feasibility of a more regular monitoring and updating strategy compared to usual practice?. In this protocol we will focus on questions one and two. METHODS: The CPG Development Programme of the Spanish Ministry of Health developed 14 CPGs between 2008 and 2009. We will stratify guidelines by topic and by publication year, and include one CPG by strata.We will develop a strategy to assess the validity of CPG recommendations, which includes a baseline survey of clinical experts, an update of the original exhaustive literature searches, the identification of key references (reference that trigger a potential recommendation update), and the assessment of the potential changes in each recommendation.We will run two alternative search strategies to efficiently identify important new evidence: 1) PLUS search based in McMaster Premium LiteratUre Service (PLUS) database; and 2) a Restrictive Search (ReSe) based on the least number of MeSH terms and free text words needed to locate all the references of each original recommendation.We will perform a survival analysis of recommendations using the Kaplan-Meier method and we will use the log-rank test to analyse differences between survival curves according to the topic, the purpose, the strength of recommendations and the turnover. We will retrieve key references from the exhaustive search and evaluate their presence in the PLUS and ReSe search results. DISCUSSION: Our project, using a highly structured and transparent methodology, will provide guidance of when recommendations are likely to be at risk of being out of date. We will also assess two novel restrictive search strategies which could reduce the workload without compromising rigour when CPGs developers check for the need of updating.

Perceptions and attitudes of clinicians in Spain toward clinical practice guidelines and grading systems: a protocol for a qualitative study and a national survey.

BACKGROUND: Clinical practice guidelines (CPGs) have become a very popular tool for decision making in healthcare. While there is some evidence that CPGs improve outcomes, there are numerous factors that influence their acceptability and use by healthcare providers. While evidence of clinicians' knowledge, perceptions and attitudes toward CPGs is extensive, results are still disperse and not conclusive. Our study will evaluate these issues in a large and representative sample of clinicians in Spain. METHODS/DESIGN: A mixed-method design combining qualitative and quantitative research techniques will evaluate general practitioners (GPs) and hospital-based specialists in Spain with the objective of exploring attitudes and perceptions about CPGs and evidence grading systems. The project will consist of two phases: during the first phase, group discussions will be carried out to gain insight into perceptions and attitudes of the participants, and during the second phase, this information will be completed by means of a survey, reaching a greater number of clinicians. We will explore these issues in GPs and hospital-based practitioners, with or without previous experience in guideline development. DISCUSSION: Our study will identify and gain insight into the perceived problems and barriers of Spanish practitioners in relation to guideline knowledge and use. The study will also explore beliefs and attitudes of clinicians towards CPGs and evidence grading systems used to rate the quality of the evidence and the strength of recommendations. Our results will provide guidance to healthcare researchers and healthcare decision makers to improve the use of guidelines in Spain and elsewhere.